What is the recommended dosing for trazodone (antidepressant medication)?

Trazodone Dosing Recommendations

For depression, start trazodone at 150 mg/day in divided doses and increase by 50 mg every 3-4 days as tolerated, with a typical therapeutic range of 150-300 mg/day for outpatients (maximum 400 mg/day) and up to 600 mg/day for inpatients. 1

Dosing for Major Depression (Primary Indication)

Initial Dosing and Titration

• Begin at 150 mg/day in divided doses, taken shortly after meals or a light snack to minimize side effects 1
• Increase by 50 mg/day every 3-4 days based on clinical response and tolerability 1
• The FDA-approved maximum for outpatients is 400 mg/day in divided doses; inpatients with severe depression may receive up to 600 mg/day 1
• Clinical evidence suggests optimal antidepressant efficacy occurs at 150-300 mg/day, with some studies showing diminished response at higher doses 2, 3

Alternative Dosing Strategy

• Single bedtime dosing is equally effective as divided doses and may improve adherence 2
• Start with 150 mg predominantly at bedtime and titrate to 200-300 mg as needed 2
• This approach reduces daytime drowsiness during initial treatment while maintaining full antidepressant efficacy 2

Duration of Adequate Trial

• Allow at least 4-8 weeks at therapeutic dose before concluding treatment failure 4
• Once adequate response is achieved, dosage may be gradually reduced with subsequent adjustments based on therapeutic response 1

Dosing for Behavioral/Sleep Disturbances (Off-Label)

For Agitation in Dementia or Behavioral Disorders

• Initial dose: 25 mg/day 5
• Maximum: 200-400 mg/day in divided doses when used as a mood-stabilizing/antiagitation agent 5, 4
• Use with caution in patients with premature ventricular contractions 5, 4

For Insomnia (Off-Label)

• Lower doses of 25-50 mg are typically employed for sleep 4
• Evidence supports 50-100 mg at bedtime, with 100 mg showing superior efficacy for sleep disorders 6
• Note: The American Academy of Sleep Medicine recommends against using trazodone for sleep onset or maintenance insomnia in adults 4

Critical Safety Considerations

Cardiac Monitoring

• Monitor for orthostatic hypotension, particularly during initial titration 4, 7
• Use caution in patients with premature ventricular contractions 5, 4
• Trazodone has notably lower cardiovascular effects compared to tricyclic antidepressants but arrhythmias require close monitoring 7

Drug Interactions

• With strong CYP3A4 inhibitors: Consider reducing dose based on tolerability 1
• With strong CYP3A4 inducers: Consider increasing dose based on therapeutic response 1

MAOI Interactions

• At least 14 days must elapse between discontinuing an MAOI and starting trazodone, and vice versa 1

Discontinuation Protocol

• Taper gradually over 10-14 days rather than stopping abruptly to limit withdrawal symptoms 4, 1
• After 9 months of treatment, consider dosage reduction to reassess the need for continued medication 4

Common Pitfalls to Avoid

• Avoid rapid titration to high doses: Studies using starting doses of 200 mg/day with rapid escalation to 600 mg/day showed poorer therapeutic responses than conservative dosing 3
• Don't skip food: Taking trazodone shortly after meals reduces side effects, though it delays absorption without affecting total drug exposure 1, 8
• Don't overlook sedation management: Administering the major portion of daily dose at bedtime or reducing total dosage can manage drowsiness 1
• Screen for bipolar disorder before initiating treatment to avoid precipitating mania 1

Special Populations

Geriatric Patients

• Maximum tolerated doses are typically 300-400 mg/day in elderly patients (compared to 600 mg/day in younger adults) 7
• Geriatric patients respond similarly to single nighttime dosing as younger patients 2
• Trazodone shows lower incidence of anticholinergic and cardiovascular effects compared to tricyclic antidepressants in the elderly 7